This laboratory is responsible for the initial observation that the feedback control of cholesterol occurs at the site of synthesis of mevalonic acid. The finding that this feedback system is consistently lost in all malignant tissues in vivo has stimulated a study of the normal metabolism of mevalonic acid under normal and pathologic conditions. We have observed that surprisingly circulating mevalonate is metabolized to cholesterol primarily in the kidney rather than in the liver as had been originally suspected. The role of the kidney in sterol metabolism has been further expanded with the observation during the past year that a "shunt" pathway of mevalonate metabolism likewise is localized to the kidney. Finally a striking sex difference in mevalonate metabolism has been recently discovered, and it is planned to determine whether the known differences in the rate of development of atherosclerosis in men and women may in part be related to the greater ability of women to metabolize mevalonate by a non-sterol pathway.